What mechanism best explains the undetectable levels of some chemotherapy drugs in leukemic cells despite treatment?

The mechanism that best explains the undetectable levels of some chemotherapy drugs in leukemic cells is the activity of the drug efflux pump, P-glycoprotein. P-glycoprotein is an ATP-dependent efflux transporter that is often overexpressed in various types of tumors, including leukemias. This protein actively transports a wide range of chemotherapeutic agents out of the cells, reducing the intracellular concentration of these drugs and thereby contributing to multidrug resistance.

The effectiveness of chemotherapy can be significantly compromised by the presence of P-glycoprotein, as it extrudes drugs before they can exert their therapeutic effects. This mechanism can lead to treatment failure despite adequate systemic drug levels, as the leukemic cells maintain low concentrations of the drug within their cytoplasm. Understanding this resistance mechanism is crucial for developing strategies to overcome drug resistance and improve the efficacy of chemotherapy in leukemic patients.